Bcl-2 family gene modulation during spontaneous apoptosis of B-chronic lymphocytic leukemia cells

• Published in: Biochemical and biophysical research communications Vol. 315; no. 3; pp. 562 - 567
• Main Authors: Sanz, Laura, Garcia-Marco, José A, Casanova, Benito, de la Fuente, Marı́a Teresa, Garcı́a-Gila, Mercedes, Garcia-Pardo, Ángeles, Silva, Augusto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.03.2004
• Subjects: Apoptosis; Apoptosis - genetics; Apoptosis Regulatory Proteins; B-CLL; B-Lymphocytes - metabolism; Bcl-2 family; Bik; Cell Line, Tumor; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Leukemic; Genes, bcl-2; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Male; Membrane Proteins - biosynthesis; mRNA expression; Neoplasm Staging; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Ribonucleases - genetics; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Bik; Apoptosis; B-CLL; Bcl-2 family; mRNA expression
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.01.095

Malignant cell accumulation in B-cell chronic lymphocytic leukemia (B-CLL) is primarily caused by defective apoptosis rather than increased proliferation. To further understand the role of Bcl-2 family members, known regulators of apoptosis, in the abnormal B-CLL survival, we have measured their mRNA levels in fresh B-CLL cells and in cultures undergoing spontaneous apoptosis. Using RNA protection assays we found constitutive expression of most bcl-2 members with high levels of bcl2, bcl-w, bad, bak, bax, and the bcl-2/bax ratio, compared to normal PBL. Spontaneous apoptosis of B-CLL cells by in vitro culture resulted in decreased bcl-2, bcl-w, bfl-1, mcl-1, bak, bax, and bcl-2/bax expression. The pro-apoptotic member bik was only expressed in 5/19 cases and was not modulated during apoptosis, suggesting that bik is not involved in this process. Thus, several Bcl-2 family genes are regulated during B-CLL spontaneous apoptosis and their relative levels may contribute to in vivo progression of the disease.